Raltegravir potassium is chemically known as N-[(4-fluorophenyl)methyl]-1,6-dihydro-5-hydroxy-1-methyl-2-[1-methyl-1-[[(5-methyl-1,3,4-oxadiazol-2-yl)carbonyl]amino]ethyl]-6-oxo-4-pyrimidine carboxamide.
Raltegravir is an antiretroviral drug used to treat HIV infection. Raltegravir targets integrase, an HIV enzyme that integrates the viral genetic material into human chromosomes, a critical step in the pathogenesis of HIV. Raltegravir potassium salt is marketed under the trade name Isentress™.
Raltegravir is disclosed in U.S. Pat. No. 7,169,780. U.S. Pat. No. '780 also discloses a process for the preparation of Raltegravir (I) by reacting acetone cyanohydrin (II) with ammonia gas in methanol to produce 2-amino-2-methylpropanenitrile (III), which is further reacted with benzylchloroformate in the presence of sodium carbonate (Na2CO3) to produce benzyl-1-cyano-1-methylethylcarbamate (IV). Compound (IV) is reacted with hydroxylamine hydrochloride in the presence of KOH in methanol to produce benzyl-2-amino-2-(hydroxyimino)-1,1-dimethylethylcarbamate (V). Compound (V) is reacted with dimethylacetylenedicarboxylate in chloroform to produce methyl-2-(1-{[(benzyloxy) carbonyl]amino}-1-methylethyl)-5,6-dihydroxypyrimidine-4-carboxylate (VI), which is treated with benzoic anhydride in the presence of pyridine to produce methyl-5-(benzoyloxy)-2-(1-{[(benzyloxy)carbonyl]amino}-1-methylethyl)-6-hydroxy-pyrimidine-4-carboxylate (VII), which is further methylated using dimethylsulfate (DMS) in the presence of lithium hydride (LiH) in dioxane to produce methyl-5-(benzoyloxy)-2-(1-{[(benzyloxy)carbonyl]amino}-1-methylethyl)-1-methyl-6-oxo-1,6-dihydroxypyrimidine-4-carboxylate (VIII). Compound (VIII) is reacted with fluorobenzylamine in methanol to produce benzyl-1-(4-{[(4-fluorobenzyl)amino]carbonyl}-5-hydroxy-1-methyl-6-oxo-1,6-dihydropyrimidin-2-yl)-1-methylethylcarbamate (IX), which is hydrogenated in the presence of Pd/C in methanol to produce 2-(1-amino-1-methylethyl)-N-(4-fluorobenzyl)-5-hydroxy-1-methyl-6-oxo-1,6-dihydropyrimidine-4-carboxamide (X). Compound (X) is condensed with 5-methyl-1,3,4-oxadiazole-2-carboxylic acid (XI) in the presence of oxalyl chloride and triethylamine in anhydrous DMF to produce Raltegravir (I).
The process is as shown in Scheme-I below:

U.S. Pat. No. '780 discloses another variant process for the preparation of Raltegravir (I) by reacting methyl-1,6-dihydro-5-(benzoyloxy)-1-methyl-2-(1-methyl-1-{[5-methyl-1,3,4-oxadiazol-2-yl)-carbonyl]amino}ethyl)-6-oxo-4-pyrimidine carboxylate (XII) with 4-fluorobenzyl amine to produce Raltegravir (I).
The process is as shown in Scheme-II below:

The major disadvantage with the above processes involves additional protection and de-protection steps for the preparation of Raltegravir. The chemical synthesis which involves more number of steps yields lower yields and the time cycle time of the production is more. This does not make the suitable for commercialization of a chemical process.
U.S. Pat. No. 7,754,731 discloses a process for the preparation of Raltegravir (I) by methylating methyl-2-(1-{[(benzyloxy)carbonyl]amino}-1-methylethyl)-5,6-dihydroxypyrimidine-4-carboxylate (VI) with methyl iodide and magnesium methoxide in dimethylsulfoxide (DMSO) and methanol to produce methyl-5-hydroxy-2-(1-{[(benzyloxy) carbonyl]amino}-1-methylethyl)-1-methyl-6-oxo-1,6-dihydroxypyrimidine-4-carboxylate (XIII), which is further condensed with p-fluorobenzylamine in ethanol to produce benzyl-1-(4-{[(4-fluorobenzyl)amino]carbonyl}-5-hydroxy-1-methyl-6-oxo-1,6-dihydro-pyrimidin-2-yl)-1-methylethylcarbamate (IX). Compound (IX) is hydrogentaed using Pd/C in the presence of methanesulfonic acid (MSA) in methanol to produce 2-(1-amino-1-methylethyl)-N-(4-fluorobenzyl)-5-hydroxy-1-methyl-6-oxo-1,6-dihydro-pyrimidine-4-carboxamide (X), which is further condensed with 5-methyl-1,3,4-oxadiazole-2-carbonyl chloride (XIa) in the presence of N-methylmorpholine (NMM) in tetrahydrofuran (THF) to produce Raltegravir (I).
The process is as shown in Scheme-III below:

The major disadvantage with the above process is that 2 equivalents acylating agent is used for the completion of acylation step. The acylating agent is more expensive and this process is not suitable for large-scale production of Raltegravir.
U.S. Pat. No. 8,686,141 discloses a process for the preparation of Raltegravir (I) by reacting benzyl-1-(4-{[(4-fluorobenzyl)amino]carbonyl}-5-hydroxy-1-methyl-6-oxo-1,6-dihydro-pyramid-in-2-yl)-1-methylethylcarbamate (IX) with pivaloyl chloride in the presence of triethylamine in ethyl acetate to produce N-[(4-fluorophenyl)methyl]-1,6-dihydro-5-pivaloyloxy-1-methyl-2-[1-methyl-1-[[(phenylmethoxy)carbonyl]amino]ethyl]-6-oxo-4-pyrimidine carboxamide (XIV).
Compound (XIV) is hydrogenated with source of hydrogen in methanol to produce N-[(4-fluorophenyl)methyl]-1,6-dihydro-5-pivalyloxy-1-methyl-2-[1-amino-1-methyl-ethyl]-6-oxo-4-pyrimidinecarboxamide (XV), which is further condensed with 5-methyl-1,3,4-oxadiazole-2-carbonylchloride (XIa) in the presence of NMM in acetonitrile to produce N-[(4-fluorophenyl)methyl]-1,6-dihydro-5-pivalyloxy-1-methyl-2-[1-methyl-1-[[(5-methyl-1,3,4-oxadiazol-2-yl)carbonyl]amino]ethyl]-6-oxo-4-pyrimidinecarboxamide (XVI). Compound (XVI) is hydrolyzed in the presence of aqueous KOH to produce Raltegravir (I).
The process is as shown in Scheme IV below:

However, there is always a need for alternative preparative routes, which for example, use reagents that are less expensive and/or easier to handle, consume smaller amounts of reagents, provide a higher yield of product, involve fewer steps, have smaller and/or more eco-friendly waste products, and/or provide a product of higher purity.
Hence, there is a need to develop cost effective and commercially viable process for the preparation of Raltegravir.